Boron trifluoride etherate → tert-Butyl 4-hydroxy-4-(3-phenylprop-2-ynyl)piperidine-1-carboxylate

HRID 1896010

Reaction equation

HRID 1896010 reaction equation
B(F)(F)F.CCOCC.[Li+].[C-:11]#[C:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[O:19]1[C:21]2([CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]2)[CH2:20]1>C1COCC1>[OH:19][C:21]1([CH2:20][C:11]#[C:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:22][CH2:23][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:25][CH2:26]1

Participants

5

Reactant 3

HCID 8000Boron trifluoride etherateHCID 3437284Lithium phenylacetylideHCID 22135564tert-Butyl 1-oxa-6-azaspiro(2.5)octane-6-carboxylate

Product 1

HCID 86627346tert-Butyl 4-hydroxy-4-(3-phenylprop-2-ynyl)piperidine-1-carboxylateYield 91.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-75 °C

Procedure

Boron trifluoride diethyl etherate (0.131 mL, 1.03 mmol) followed by lithium phenylacetylide (1M in THF, 1.03 mL, 1.03 mmol) was dropped into a solution of Compound 256a (200 mg, 0.938 mmol) in THF (5 mL) stirred at −75° C. under nitrogen atmosphere. Stirring and cooling were kept on for 2 h and after overnight stirring at r.t., the reaction mixture was quenched with water and EtOAc. The combined extracts were washed, dried over Na2SO4 and evaporated to dryness. The residue was purified by flash chromatography (EtOAc—Petroleum Ether 85:15) affording the title product (272 mg).

Workup

  1. stirringStirring
  2. temperaturecooling
  3. stirringstirring at r.t.
  4. customthe reaction mixture was quenched with water and EtOAc
  5. washThe combined extracts were washed
  6. dry with materialdried over Na2SO4
  7. customevaporated to dryness
  8. customThe residue was purified by flash chromatography (EtOAc—Petroleum Ether 85:15)

Sources & evidence

ORD record
ord-aad17222f93344df9a3fc42be36177bf
Source dataset
uspto-grants-2013_08
Patent number
US08518916B2

Linked notes

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